Research

The Integrative Cartilage Research Group employs innovative biomedical engineering approaches to investigate mechanobiological-signalling networks in cartilage and joint disorders and provide strategies for repair, specifically for arthritis and craniofacial defect studies.


Micro-computed Tomography for Structure-Function Investigation

The ICRG approach uses micro-computed tomography with novel contrast agents (31), other imaging modalities (4,9), imaging protocols (16) and processing methods to capture detailed structural information of organs, tissues and cells, and then links this to materials analyses; via mechanical testing and assays, to provide unique insight into the structure-function relationships. For example, in joints (5,7,25), ears (21), and tissue-engineered constructs (15).


Quantitative Morphometric Analysis (QMA) & Image Processing

Quantitative Morphometric Analysis uses high-resolution image data to extract measurements of clinical or preclinical importance. These may be healthy and diseased structures of specific importance to the system being studied; for example, small animal joints (30, 33) for drug discovery, human clinical trials (35-38), or disease investigation (27).


Biofabrication & Tissue Engineering

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Working with partners in materials synthesis and fabrication approaches, as well as tissue engineering of musculoskeletal tissues, we investigate approaches for more efficient, effective and nascent tissue production. This includes exploring bioprinting (13), electrospinning (34), decellularisation (23), sterilisation (17), and material-doping (10, 14) approaches.


Mechanobiology & Remodelling

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The link between tissue composition and architecture with the resulting tissue function and integrity requires a deep understanding of the communication between biological, mechanical, and structural components of the cells (8, 20) and tissues (1-3, 11, 19, 28, 32). This is true for both engineered (6) and native tissues (29). In this work, we explore native communication pathways and develop new approaches for manipulating these in repair (12, 18, 26) and reconstruction studies (24).


Publications:

38. K. S. Stok, S. Finzel, A. J. Burghardt, P. G. Conaghan, C. Barnabe. The SPECTRA Collaboration (Study grouP for xtrEme-Computed Tomography in Rheumatoid Arthritis) OMERACT Special Interest Group – Current Research and Future Directions, J Rheum, 44, 2017.

37. S. Tom, M. Frayne, S. L. Manske, A. J. Burghardt, K. S. Stok, S. K. Boyd, and C. Barnabe, Determining Metacarpophalangeal Flexion Angle Tolerance for Reliable Volumetric Joint Space Measurements by High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT), J Rheum, 43:1941-44, 2016.

36. C. Barnabe, D. Toepfer, H. Marotte, E.M. Hauge, A. Scharmga, R. Kocijan, S. Kraus, S. Boutroy, K. Karup Keller, J. de Jong, J. Williams, K. S. Stok, S. Finzel, Definition for Rheumatoid Arthritis Erosions Imaged with High Resolution Peripheral Quantitative Computed Tomography and Inter-Reader Reliability for Detection and Measurement, J Rheum, 43:1935-40, 2016.

35. S. Nagaraj, S. Finzel, K.S. Stok, C. Barnabe and the SPECTRA Collaboration, High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) Imaging in the Assessment of Periarticular Bone of Metacarpophalangeal and Wrist Joints, J Rheum, 43:1921-34, 2016.

34. J. Walser, K.S. Stok, M.D. Caversaccio, and S.J. Ferguson. Direct electrospinning of 3D auricle-shaped scaffolds for tissue engineering applications, Biofabrication, 8(2):025007, 2016.

33. K. S. Stok, B. A. Besler, T. H. Steiner, A. V. Villarreal Escudero, M. A. Zulliger, M. Wilke, K. Atal, A. Quintin, B. Koller, R. Müller and D. Nesic. Three-dimensional quantitative morphometric analysis (QMA) for in situ joint and tissue assessment of osteoarthritis in a preclinical rabbit disease model, PLoS One, 11(1): e0147564, 2016.

32. L. Nimeskern, L. Utomo, I. Lehtoviita, G. Fessel, J. G. Snedeker, G. J.V.M van Osch, R. Müller, K. S. Stok, Tissue composition regulates distinct viscoelastic responses in auricular and articular cartilage, J. Biomech, 49(3):344-352, 2016.

31. B. A. Lakin, H. Patel, C. Holland, J. D. Freedman, J. S. Shelofsky, B. D. Snyder, M. W. Grinstaff and K. S. Stok. Contrast-enhanced CT using a cationic contrast agent enables non-destructive assessment of the biochemical and biomechanical properties of mouse tibial plateau cartilage, J. Orthop Res, 34(7):1130-1138, 2016.

30. B. A. Besler, R. E. Sondergaard, R. Müller and K. S. Stok, Reproducibility of compartmental subchondral bone morphometry in the mouse tibiofemoral joint, Bone, 81(12):649–653, 2015.

29. L. Nimeskern, M. M. Pleumeekers, D. J. Pawson, W. L. M. Koevoet, I. Lehtoviita, M. B. Soyka, C. Röösli, D. Holzmann, G. J. V. M. van Osch, R. Müller and K. S. Stok. Mechanical and biochemical mapping of human auricular cartilage for reliable assessment of tissue-engineered constructs, J Biomech, 48(10): 1721–1729, 2015.

28. M. M. Pleumeekers, L. Nimeskern, W. L. M. Koevoet, M. Karperien, K. S. Stok and G. J. V. M. van Osch. Cartilage regeneration in the head and neck area: Combination of ear or nasal chondrocytes and mesenchymal stem cells improves cartilage production, Plast Reconstr Surg, 136(6): 762e-74e, 2015.

27. D. J. Pawson, M. Glanzmann, R. Lüchinger, R. Müller, K. S. Stok, Quantitative morphometric patterns in cartilage and bone from the humeral heads of end-stage osteoarthritis patients. Osteoarthr Cartilage, 23:1377-1387, 2015.

26. N. M. Kogan, E. Melamed, E. Wasserman, B. Raphael, A. Breuer, K. S. Stok, R. Sondergaard, A. V. Villarreal Escudero, S. Baraghithy, M. Attar-Namdar, S. Friedlander-Barenboim, N. Mathavan, H. Isaksson, R. Mechoulam, R. Müller, A. Bajayo, Y. Gabet and I. Bab, Cannabidiol, a major non-psychotrophic cannabis constituent enhances fracture healing and stimulates lysyl hydroxylase activity in osteoblasts, JBMR, 30(10):1905-1913, 2015.

25. C. Barnabe, S. Finzel, K. S. Stok, P. Geusens, Invited correspondence “High-resolution peripheral quantitative CT in rheumatology”, Nature Rev Rheum, 11(2):123, 2015.

24. H. Martínez Ávila, E. Feldmann, M. M. Pleumeekers, L. Nimeskern, W. Kuo, W. C. de Jong, S. Schwarz, R. Müller, J. Hendriks, N. Rotter, G.J.V.M. van Osch, K. S. Stok and P. Gatenholm, Novel bilayer bacterial nanocellulose scaffold supports neocartilage formation in vitro and in vivo. Biomaterials, 44:122-133, 2015.

23. L. Utomo, M. M. Pleumeekers, L. Nimeskern, S. Nürnberger, K. S. Stok, F. Hildner, G. J.V.M. van Osch, Processing and characterization of a decellularized cartilage scaffold for ear cartilage reconstruction, Biomedical Materials, 10(1), 015010, 2015.

22. L. Nimeskern, N. Rotter, G.J.V.M van Osch, R. Müller and K. S. Stok, Response to Letter to the Editor Concerning, “Quantitative evaluation of mechanical properties in tissue-engineered auricular cartilage”, Tissue Eng Part B Rev. 21(2): 244-245, 2015.

21. L. Nimeskern, E. M. Feldmann, S. Schwarz, W. Kuo, S. Duerr, E. Goldberg-Bockhorn, R. Müller, N. Rotter, K. S. Stok, Magnetic Resonance Imaging of the ear for patient-specific reconstructive surgery, PLoS One, 9(8): e104975, 2014.

20. M.M. Pleumeekers, L. Nimeskern, W.L.M. Koevoet, N. Kops, R.M.L. Poublon, K. S. Stok, G.J.V.M. van Osch, The in vitro and in vivo capacity of culture-expanded human cells from several sources encapsulated in alginate to form cartilage. Eur. Cells. Mater, 27:265-280, 2014.

19. L. Nimeskern, G.J.V.M van Osch, R. Müller and K. S. Stok. Quantitative evaluation of mechanical properties in tissue-engineered auricular cartilage. Tissue Eng. Part B Rev., 20(1):17-27, 2014.

18. F. Rikhtegar, C. Wyss, K. S. Stok, D. Poulikakos, R. Müller and V. Kurtcuoglu. Hemodynamics in coronary arteries with overlapping stents. J. Biomech., 47(1):505-511, 2014.

17. S. Hofmann, K. S. Stok, T. Kohler, A. J. Meinel, and R. Müller. Sterilization effects on structure and properties of 3D silk fibroin scaffolds, Acta Biomat., 10(1):308-317, 2014.

16. R. J. Choo, R. Müller and K. S. Stok. Prevention of cartilage dehydration in imaging studies with a customised humidity chamber. Rev. Sci. Instrum., 84(9), 093703, http://dx.doi.org/10.1063/1.4820913, 2013.

15. W. Kuo, L. Nimeskern, H. Martínez Ávila, S. Hofmann, J. Freedman, M. W. Grinstaff, R. Müller, K. S. Stok. Developing staining protocols for visualization of tissue-engineering scaffolds using micro computed tomography in native wet state. Proc. Gemeinsame Jahrestagung der Deutschen, österreichischen und Schweizerischen Gesellschaft für Biomedizinische Technik, Graz, Austria, September 19-21, Biomed. Tech., 58(S1):4273, 2013.

14. D. Loessner, S. C. Rizzi, K. S. Stok, T. Fuhrman, B. Hollier, V. Magdolen, D. W. Hutmacher and J. A. Clements. A bioengineered 3D ovarian cancer model for the assessment of peptidase-mediated enhancement of spheroid growth and intraperitoneal spread. Biomaterials, 34(30):7389-7400, 2013.

13. L. Nimeskern, H. Martinez, J. Sundberg, P. Gatenholm, R. Müller and K. S. Stok. Mechanical evaluation of bacterial nanocellulose as an implant material for ear cartilage replacement. J. Mech. Behav. Biomed., 22C:12-21, 2013.

12. F. Rikhtegar, F. Pacheco, C.Wyss, K. S. Stok, H. Ge, R. J. Choo, A. Ferrari, R. Müller, D. Poulikakos, and V. Kurtcuoglu, Compound ex vivo and in silico method for hemodynamic analysis of stented arteries, PLoS One, 8(3):e58147,2013.

11. E. Schuh, S. Hofmann, K. S. Stok, H. Notbohm, R. Müller and N. Rotter. The influence of matrix elasticity on chondrocyte behaviour in 3D. J. Tissue Eng. Regen. M., 6(10):e31-e42, 2012.

10. E. Schuh, S. Hofmann, K. S. Stok, H. Notbohm, R. Müller and N. Rotter. Chondrocyte redifferentiation in 3D: the effect of adhesion site density and substrate elasticity. J. Biomed. Mater. Res. A, 100 (1): 38-47, 2012.

9. J. P. Moodie, K. S. Stok, R. Müller, T. L. Vincent and S. J. Shefelbine. Multimodal imaging demonstrates concomitant changes in bone and cartilage after destabilisation of the medial meniscus and increased joint laxity. Osteoarthr Cartilage, 19:163-170, 2011.

8. D. Loessner, K. S. Stok, M. P. Lutolf, D. W. Hutmacher, J. A. Clements, S. C. Rizzi. Bioengineered 3D platform to explore cell–ECM interactions and drug resistance of epithelial ovarian cancer cells, Biomaterials, 31(32): 8494-8506, 2010.

7. K. S. Stok, D. Noël, F. Apparailly, D. Gould, Y. Chernajovsky, C. Jorgensen and R. Müller. Quantitative imaging of cartilage and bone for functional assessment of gene therapy approaches in experimental arthritis. J. Tissue Eng. Regen. Med., 4:387-394, 2010.

6. K. S. Stok, S. Cristino, G. Lisignoli, A. Facchini and R. Müller. Mechano-functional assessment of human mesenchymal stem cells grown in three-dimensional hyaluronan-based scaffolds, J. Biomed. Mater. Res. A, 93A(1):37-45, 2010.

5. K. S. Stok, G. Pelled, Y. Zilberman, I. Kallai, D. Gazit, and R. Müller. Revealing the interplay of bone and cartilage in osteoarthritis through multimodal imaging of murine joints, Bone, 45:414-422, 2009.

4. K. S. Stok, and R. Müller. Morphometric characterisation of murine articular cartilage – Novel application of confocal laser scanning microscopy, Microsc. Res. Techniq., 72:650-658, 2009.

3. K. S. Stok, and A. Oloyede. Conceptual fracture parameters for articular cartilage, Clinical Biomechanics, 22(6), 2007.

2. K. S. Stok, and A. Oloyede. A qualitative analysis of crack propagation in articular cartilage at varying rates of tensile loading, Connect Tissue Res, 44 (2), 2003.

1. K. S. Stok, and A. Oloyede. Dependence of the biomechanical responses of the trabecular bone on density and strain-rate under torsional loading, The Journal of Locomotor Systems, 7 (4), 2000.